1,2-Benzenediol, 4-[(4-methylphenyl)sulfonyl]-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(4-hydroxyphenyl)benzenesulfonamide

EC Number:

654-333-7

Cas Number:

5471-90-9

Molecular formula:

C12 H11 N O3 S

IUPAC Name:

N-(4-hydroxyphenyl)benzenesulfonamide

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han); Outbred, SPF-Quality

Sex:

female

Details on test animals or test system and environmental conditions:

Test animals
Source:
Charles River Deutschland, Sulzfeld, Germany
Number of Animals:
3 females (nulliparous and non-pregnant)
Age at the Initiation of Dosing:
Young adult animals (approximately 10-11 weeks old) were selected.
Weight at the Initiation of Dosing:
194 to 199 g.

Animal Identification
At study assignment, each animal was identified using a tail mark with indelible ink.

Environmental Acclimation
The animals were allowed to acclimate to the Test Facility toxicology accommodation for at least 5 days before the commencement of dosing.

Housing
On arrival, animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) and following assignment to the study, animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. The room in which the animals were kept was documented in the study records.
Animals were separated during designated procedures/activities. Each cage was clearly labeled.

Environmental Conditions
Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were maintained. The actual daily mean temperature during the study period was 20 to 21°C with an actual daily mean relative humidity of 48 to 53%. A 12 hour light/12 hour dark cycle was maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.

Food
Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.
The feed was analyzed by the supplier for nutritional components and environmental contaminants. Results of the analysis were provided by the supplier and are on file at the Test Facility.
It is considered that there were no known contaminants in the feed that would interfere with the objectives of the study.

Water
Municipal tap-water was freely available to each animal via water bottles.
Periodic analysis of the water was performed, and results of these analyses are on file at the Test Facility.
It is considered that there were no known contaminants in the water that would interfere with the objectives of the study.

Animal Enrichment
For psychological/environmental enrichment, animals were provided with paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom), except when interrupted by study procedures/activities.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1% Aqueous carboxymethyl cellulose

Details on dermal exposure:

Administration of Test item
A single dose of test item was administered to the appropriate animals by dermal application on Day 1. One day before dosing, an area of approximately 5x7 cm on the back of the animals was clipped. The test item was applied in an area of approximately 10% of the total body surface, i.e. approximately 18 cm² for females. The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only. The application period was 24 hours, after which the dressing was removed and the skin cleaned of residual test item using water.
The dose volume for each animal was based on the body weight measurement prior to dosing. A dose volume of 10 mL/kg body weight will be used for each dose.
The dosing formulations were stirred continuously during dose administration.

Justification of Route and Dose Levels
The dermal route was selected as it is a possible route of human exposure during manufacture, handling or use of the test item. The dose levels were based on the OECD test guidelines.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Mortality/Moribundity Checks
Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.

Clinical Observations
Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days.
All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals during and for the first hour after dosing.
Animals were weighed individually on Day 1 (pre-dose), 8 and 15.
The skin reactions were assessed approximately 24, 48 and 72 hours after the removal of the dressing and test item. Adjacent areas of untreated skin of each animal served as controls.

Terminal Procedures
All animals were sacrificed by oxygen/carbon dioxide procedure at the end of the observation period. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

No statistics were applied

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality occurred

Clinical signs:

other: Ptosis was noted for one animal on Day 1 and hunched posture was noted for two animals on Day 2.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of CH03951 in Wistar Han rats was established to exceed 2000 mg/kg body weight.
Based on these results, CH03951 does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Executive summary:

The objective of this study was to determine the potential toxicity of CH03951, when given by a single dermal dose.

The study was carried out based on the guideline described in:

·     OECD No. 402 (2017) "Acute Dermal Toxicity".

CH03951 was administered to three female Wistar Han rat by a single dermal application at 2000 mg/kg body weight for 24 hours. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed or after terminal sacrifice (Day 15).

No mortality occurred.

Ptosis was noted for one animal on Day 1 and hunched posture was noted for two animals on Day 2. No signs of irritation was noted for any of the animals at any time point.

The body weights shown by the animals during the observation period was within the range expected for rats used in this type of study.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of CH03951 in Wistar Han rats was established to exceed 2000 mg/kg body weight.

Based on these results, CH03951 does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).